Effect of BMP2-Platelet-rich Plasma-Biphasic Calcium Phosphate Scaffold on Accelerated Osteogenesis in Mastoid Obliteration.

The aim of this study was to evaluate the synergistic effect of platelet-rich plasma (PRP) and recombinant human bone morphogenic protein (BMP)-2 on accelerated osteogenesis of hydroxyapatite/ß-tricalcium phosphate mixture and biphasic calcium phosphate (BCP) in mastoid obliteration. To the best of our knowledge, there have been no studies reporting the enhancing effects of BCP, combined with BMP2 and PRP, on osteogenesis in mastoid obliteration. Mastoid obliteration was performed in a control group (BCP only, n=7), a group treated with BMP2 and BCP (experimental group I, n=7), and a group treated with BMP2, PRP and BCP (experimental group II, n=7). The animals were administered fluorescent bone labels for a qualitative evaluation of bone formation; oxytetracycline hydrochloride was administered at 2 weeks, calcein at 4 weeks, and alizarin red at 8 weeks. The animals were sacrificed 12 weeks post-surgery and osteogenesis was evaluated by micro-computed tomography, histological investigation, and histomorphometry. Both experimental groups showed accelerated osteogenesis compared to the control group. However, there were no statistically significant differences between experimental groups I and II. From these results, it can be concluded that BMP2 activated BCP for the enhancement of bone regeneration. However, no synergistic effect of BMP2 and PRP on the osteogenesis of BCP was observed.

Congestion of mastoid mucosa and influence on middle ear pressure - Effect of retroauricular injection of adrenaline.

Micro-CT scanning of temporal bones has revealed numerous retroauricular microchannels, which connect the outer bone surface directly to the underlying mastoid air cells. Their structure and dimensions have suggested a separate vascular supply to the mastoid mucosa, which may play a role in middle ear (ME) pressure regulation. This role may be accomplished by changes in the mucosa congestion resulting in volumetric changes, which ultimately affect the pressure of the enclosed ME gas pocket (Boyle's law). Further, such mucosa congestion may be susceptible to α-adrenergic stimulation similar to the mucosa of the nose. The purpose of our study was to investigate these hypotheses by recording the ME pressure in response to adrenergic stimulation administered by retroauricular injections at the surface of the microchannels. In a group of 20 healthy adults we measured the ME pressure by tympanometry initially in the sitting position, and then in the supine position over a 5 min period with 30 s intervals. In each subject, the study included 1) a control reference experiment with no intervention, 2) a control experiment with subcutaneously retroauricular injection of 1 ml isotonic NaCl solution, and 3) a test experiment with subcutaneously retroauricular injection of 1 ml NaCl-adrenaline solution. In both control experiments the ME pressure displayed an immediate increase in response to changing body position; this pressure increase remained stable for the entire period up to five minutes. In the test experiments the ME pressure also showed an initial pressure increase, but it was followed by a distinct significant pressure decrease with a maximum after 90 s. The test group was injected with both a 5 and 10% adrenaline solution, but the responses appeared similar for the two concentrations. Subcutaneous retroauricular injection of adrenaline caused a significant pressure decrease in ME pressure compared with control ears. This may be explained by the microchannels conveying the adrenaline to the underlying mastoid mucosa, where it may result in a vascular constriction and decongestion, ultimately resulting in a ME pressure decrease. These findings suggest that the microchannels contain vascular connections to the mastoid mucosa, and that the mastoid mucosa is susceptible to vasoactive mediators, which may play a role in ME pressure regulation. Further anatomical and physiological experiments should be carried out to confirm these suggestions including pharmacological interactions with the mastoid mucosa.

Complications in cochlear implant surgery.

UNLABELLED: For the last 6 years, cochlear implantation has become a standard practice in our department. The number of patients rose from 5 to 21/ year. Using multiple types of cochlear implants and indicating the surgery also to malformed inner ears led to the encounter of some complications. OBJECTIVE: to present the surgical complications from our department. MATERIAL: all the patients admitted and operated in our clinic have been reviewed. RESULTS: 9 complications (8,86%) have occurred: the impossibility of establishing a reliable cochleostomy (due to ossification), air in the cochlea through lack of sealing of the cochleostomy (exteriorization of the electrode array), cochlear implant postoperative migration from its bed, weak hearing discrimination due to "double electrodes" in the scala tympani, gusher. CONCLUSIONS: cochlear implanting needs to respect the technical steps of the surgery and the best technical/ tactical solution has to be found to whatever complications arise in complex or malformed cases!

Mastoid obliteration using three-dimensional composite scaffolds consisting of polycaprolactone/ß-tricalcium phosphate/collagen nanofibers: an in vitro and in vivo study.

Two different composite scaffolds, solid-freeform-fabricated PCL/ß-TCP supplemented with and without collagen nanofibers are fabricated. These scaffolds are evaluated whether a combination of collagen nanofibers with PCL/ß-TCP can promote osteogenesis in a mastoid obliteration. To assess the effects of the cellular activities of osteoblast-like-cells (MG63), SEM images and MTT assays are conducted. Experimental mastoid obliteration is performed using guinea pigs that are divided group A (PCL/ß-TCP/collagen-nanofiber scaffold) and group B (PCL/ß-TCP scaffold). The results reveal that PCL/ß-TCP/collagen scaffold provide much broader cell attachment sites than PCL/ß-TCP scaffold. The µ-CT and fluorescent microscopy results reveal that the acceleration of early new bone formation within the pores and scaffold itself at week 4 post-operation is more effective in group A. In addition, based on the results of the histological and µ-CT at 12 weeks post-surgery, the effective regeneration of bone in the PCL/ß-TCP/collagen scaffold is appeared.

Regeneration of mastoid air cells using polycaprolactone/ß-tricalcium phosphate biocomposites: an experimental study.

OBJECTIVES/HYPOTHESIS: The study aimed to regenerate pneumatic air cells in guinea pig bulla using three-dimenisonal (3D) biocomposite scaffolds consisting of polycaprolactone/ß-tricalcium phosphate (PCL/ß-TCP). STUDY DESIGN: Prospective controlled study in experimental animals. METHODS: PCL/ß-TCP composites were implanted into the bulla with mucosa preservation in group A (n = 10). PCL/ß-TCP composites coated with collagen were implanted in group B (n = 10). After 12 weeks, the bullae were extracted and evaluated by micro-computed tomography (micro-CT) and were processed for histological analyses. RESULTS: In group A, micro-CT showed a well-maintained honeycomb appearance of micropores without obstruction. Regeneration of the mucosa was noted inside the pores of the 3D scaffold. However, partial obstruction of the micropores with new bone formation was evident in group B. CONCLUSIONS: Group A showed more satisfactory mucosal regeneration into the micropores. Our results indicate that the 3D scaffold may be amenable for use during mastoidectomy. Further studies for gas exchange in the regenerated mucosa are necessary.

Obliteration of temporal dorsal bulla in guinea pigs using different types of calcium phosphate.

OBJECTIVE: The purpose of this study was to evaluate the applicability of different calcium phosphate types after mastoid obliteration procedure using the guinea pig as an animal model. MATERIALS AND METHODS: Twenty six male guinea pigs were used for the experimental study. Four guinea pigs were used as a normal control group, with the remaining used for the experimental group. After bulla mucosa was removed, non-obliterated ears were used as control and granular (Polybone-G) or powder (Polybone-P) types of Polybone (tricalicium phosphate and polyphosphate) were applied into the dorsal bulla. The radiological and histologic findings were obtained from each animal at 8 and 20 weeks after obliteration. RESULTS: On radiological examination, thickening of the bulla wall observed in all experimental groups compared with normal group. Increased homogenous bony densities continuous with the bulla wall were observed in the Polybone-G group compared to the other experimental groups, and some isolated bony densities were observed in the Polybone-P group. Histopathologic findings showed increased new bone formations and less inflammatory reactions in the Polybone-G group compared to the Polybone-P group. CONCLUSION: This study demonstrates that granular type calcium phosphate can be used as effective material than powder type in mastoid obliteration.

Effect of piperacillin-tazobactam coated ß-tricalcium phosphate for mastoid obliteration in otitis media.

BACKGROUND AND OBJECTIVE: ß-Tricalcium phosphate (TCP) has good biodegradability and osteoconductivity as a scaffold material for bone tissue engineering. Both block and granular forms are available; however, it has been associated with risk of infection and exposure. To this end, the study evaluated the effect of piperacillin-tazobactam coated ß-TCPs for mastoid obliteration in otitis media. MATERIALS AND METHODS: Ten guinea pigs were divided into the experimental (piperacillin-tazobactam coated ß-TCP granules, n=5) and control groups (uncoated ß-TCP granules, n=5). After mastoid obliteration, transtympanic injection with a saline suspension of lipopolysaccharide established inflammation. The animals were sacrificed 5 weeks later. Tissue sections were stained with hematoxylin and eosin and examined. RESULTS: Encapsulation and formation of fibrous capsule by foreign material in the bulla were not evident. The histological evaluation did not reveal inflammatory cells and fibrosis in the piperacillin-tazobactam coated ß-TCP group. In contrast, the control group showed numerous inflammatory cells around the implanted uncoated ß-TCP granules and incomplete new bone formation. CONCLUSION: ß-TCP is an effective carrier material for piperacillin-tazobactam. The use of piperacillin-tazobactam coated ß-TCP may be optimal for mastoid obliteration.

Histopathologic changes in guinea pig mastoid mucosa after topical mitomycin C application followed by mastoidectomy.

PURPOSE: This study was performed to investigate the histopathologic changes observed in mastoid cavity of guinea pigs after the application of mitomycin C after mastoidectomy. MATERIALS AND METHODS: The study was performed on 50 guinea pigs. Unilateral (right ear) mastoidectomy was performed on all guinea pigs. Twenty-five guinea pigs were separated as study group and the remaining were separated as control group. A mitomycin C-soaked sponge was placed in the mastoid cavities of the study group and a dry sponge was placed in those of the control group. Their mastoid cavities were examined histopathologically for absorbable sponge waste, abscess formation, fibrosis, vascularization, polymorphonuclear leukocyte infiltration, edema, lymphoplasmacytic inflammatory infiltration, and granulation tissue. RESULTS: Absorbable sponge waste, abscess formation, fibrosis, vascularization, edema, and lymphoplasmacytic inflammatory infiltration were not significantly different between the groups. However, polymorphonuclear leukocyte infiltration and granulation tissue were statistically different between the groups. CONCLUSION: Mitomycin C can be used after mastoidectomy to decrease the granulation tissue formation in ear discharges and to prevent the discharge.

Experimental studies on a new highly porous hydroxyapatite matrix for obliterating open mastoid cavities.

OBJECTIVE: In an initial preliminary study, the applicability of a new high-porosity hydroxyapatite (HA) ceramic for obliterating large open mastoid cavities was proven and tested in an animal model (bulla of guinea pig). STUDY DESIGN: Experimental study. METHODS: NanoBone, a highly porous matrix consisting of 76% hydroxyl apatite and 24% silicone dioxide fabricated in a sol-gel technique, was administered unilaterally into the opened bullae of 30 guinea pigs. In each animal, the opposite bulla was filled with Bio-Oss, a bone substitute consisting of a portion of mineral bovine bone. Histologic evaluations were performed 1, 2, 3, 4, 5, and 12 weeks after the implantation. RESULTS: After an initial phase in which the ceramic granules were surrounded by inflammatory cells (1-2 wk), there were increasing signs of vascularization. Osteoneogenesis and-at the same time-resorption of the HA ceramic were observed after the third week. No major difference in comparison to the bovine bone material could be found. DISCUSSION: Our results confirm the favorable qualities of the new ceramic reported in association with current maxillofacial literature. Conventional HA granules used for mastoid obliteration to date often showed problems with prolonged inflammatory reactions and, finally, extrusions. In contrast to those ceramics, the new material seems to induce more osteoneogenesis and undergoes early resorption probably due to its high porosity. Overall, it is similar to the bovine bone substance tested on the opposite ear in each animal. Further clinical studies may reveal whether NanoBone can be an adequate material for obliterating open mastoid cavities in patients.

Preservation of the mastoid aeration and prevention of mastoid dimpling in chronic otitis media with cholesteatoma surgery using hyaluronate-based bioresorbable membrane (Seprafilm).

During mastoidectomy a hollow-cavity is formed within the mastoid bone after its cortex and air cells are removed. Postoperatively, the aerated cavity is usually filled with soft tissues. Also it is not so uncommon to see cases with retraction of the mastoid area skin into the cavity causing a cosmetic problem termed as mastoid dimpling. In order to achieve an aerated mastoid cavity and minimizing the mastoid dimpling, an adhesion barrier was utilized to prevent fibrous tissue formation within the cavity. Twenty-one patients with middle ear and/or mastoid cholesteatoma, who underwent tympanoplasty with mastoidectomy (canal wall-up) with staged procedures, were included in the study. The mastoid cavity was tented and covered with an adhesion barrier (hyaluranic acid and carboxymethylcellulose, Seprafilm, (Seprafilm, GENZYME Inc., Cambridge, MA, USA) at the end of the surgery. Postoperatively, in two cases serohemorrhagic fluid collected between the adhesion barrier membrane and the subcutaneous tissues requiring drainage. Second stages were performed 4-6 months after the first stage. Two residual cholesteatoma cases were present. Patients were followed for a minimum of 2 years after the second stage. Mean follow-up was 2 years and 5 months. No wound infection was encountered postoperatively. Late follow-up of minimum 2 years after the second surgery revealed cosmetically acceptable retroauricular area with no dimpling. Mild retraction in two cases and two micro-central perforations in the neotympanic membrane were found. CT scans obtained both prior to the second stage and at the end of the second year of second stage revealed fully aerated mastoid cavities covered with periosteum in its natural position. Mastoid cortex plasty with seprafilm offers a rapid and effective solution to the preservation of mastoid space and the preservation of the contours of the mastoid bone.

Otologic effects of topical mitomycin C: phase I-evaluation of ototoxicity.

HYPOTHESIS: To determine ototoxicity of topical mitomycin C when placed in the middle ear at varying concentrations. BACKGROUND: Despite meticulous surgical technique and diligent postoperative care, some patients develop excessive scar and granulation tissue in the middle ear or mastoid cavity. Poor wound healing may result in infection, tympanic membrane perforation, or conductive hearing loss, which may necessitate further surgery. Use of topical mitomycin C in the ear may be beneficial in reducing scar and granulation tissue formation. This phase of the study was developed to determine the safety of topical mitomycin C in the rat model relative to ototoxicity. METHODS: Twelve Sprague-Dawley rats were evaluated with auditory brainstem response testing before and after treatments. Topical mitomycin C was injected in the middle ear of the right ear of eight animals. Varying concentrations of 0.125 to 0.5 mg/ml were used. Saline was injected in the left ear of each animal to serve as a control. Four separate animals were evaluated with placement of topical mitomycin C on Gelfoam into the middle ear. In two animals, Gelfoam was placed in the middle ear for 1 minute and then removed. In two animals, Gelfoam was placed in the middle ear and left in place. Auditory brainstem response testing was performed at 4 weeks and at 8 weeks. RESULTS: Using a high concentration of mitomycin C (>0.25 mg/ml) resulted in ototoxicity, with an increase in the auditory brainstem response threshold at 4 weeks and at 8 weeks. At low concentrations (<0.20 mg/ml), no change in auditory brainstem response threshold was noted. Animals treated with Gelfoam soaked in mitomycin C showed no change in auditory brainstem response threshold. CONCLUSION: The results of this study indicate that topical mitomycin C on Gelfoam applied in the middle ear appears safe when low concentrations are used, even in the rat, which has a higher susceptibility to gentamycin toxicity than humans. Higher concentrations may lead to ototoxicity based on changes in Wave V on auditory brainstem response. This treatment may prove to be an important option for patients suffering from chronic granulation tissue or scar tissue in the external or middle ear.

Reconstruction of mastoid cortex defect using bone morphogenetic protein: an experimental study in the guinea pig.

OBJECTIVE: The aim of this experimental study was to examine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) could induce new bone formation in a small hole drilled through the temporal bone near the external auditory canal wall in guinea pigs. MATERIAL AND METHODS: A 4-mm diameter hole was made in the center of the temporal bone and a piece of collagen sheet infiltrated with rhBMP-2 was placed in the hole. New bone formation was confirmed by means of X-ray examination and the bone mineral density was quantified using dual-energy X-ray absorptiometry 1, 2 and 4 weeks after treatment. RESULTS: The bone mineral density in the rhBMP-2-treated group was significantly increased compared to the control group. CONCLUSION: These results suggest that rhBMP-2 induces remarkable new bone formation in the temporal bone and will be useful in clinical ear surgery.

Mastoid obliteration by BMP-2/collagen composites: an experimental study using tissue engineering.

PURPOSE: Several materials have been used in the application of mastoid cavity obliteration during surgery for cholesteatoma; however, nothing has won universal acceptance. Through the advancement of tissue engineering, bone morphogenetic protein-2 (BMP-2)/collagen composites have been elucidated as inducers of heterogenic bone formation. This study was performed to investigate whether these composites are potentially obliteration materials for use in the mastoid cavity by using an animal experimental study. MATERIALS AND METHODS: The composites were implanted in the rat mastoid to investigate whether new bone would be tissue engineered in the mastoid and, if so, whether the newly formed bone was stable. The composites were examined histologically over a 24-week period. RESULTS: The composites implanted in the rat mastoid were able to tissue engineer new bone, and the newly formed bone was stable as assessed histologically, with almost normal bone structure, that was not resorbed during the 24-week period. Adverse immunological reactions were not found during our observation. CONCLUSIONS: Bone that was tissue engineered by the BMP-2/collagen composites was stable as assessed by histological examination and persisted in the rat mastoid. The present study shows that the composites have the potential to become real materials for use in mastoid obliteration.

Middle ear pressure variations during 50% N2O anesthesia as a function of mastoid pneumatization.

HYPOTHESIS: Mastoid size is a factor in middle ear (ME) pressure regulation. BACKGROUND: In a study investigating ME pressure variations during nitrous oxide (N2O) anesthesia, particularly high values of ME pressure increase rate (PIR) were observed in four patients with sclerotic mastoids. The current study is aimed at systematically assessing this observation. METHODS: Middle ear pressure was measured periodically in 30 patients during 50% N2O anesthesia using tympanometry. For each patient, a curve representing ME pressure during anesthesia was plotted. From the curve steepness, the PIR was calculated. Extent of mastoid pneumatization was assessed planimetrically using mastoid x-rays. Ears then were divided by the median into two groups: ears with small mastoids and ears with large mastoids. The difference between the mean PIR of both ear groups was statistically analyzed. RESULTS: A significant difference between the PIR was found among the two groups. In ears with mastoids smaller than 9.475 cm2 (the median), the PIR was significantly higher than in ears with mastoids > 9.475 cm2. CONCLUSIONS: These findings support the concept that the mastoid has a ME pressure buffering capability: the larger its volume, the better its buffering capability. It is therefore suggested, that the mastoid plays a role in ME pressure regulation.

Neurotologic presentation of sagittal sinus thromboses associated with oral contraceptive usage.

Thrombosis of the cerebral venous sinuses has long been a recognized complication of late stage pregnancy and the puerperium; more recently, this complication has been associated with the use of oral contraceptives. Two cases are presented in which the presenting symptoms of sagittal sinus thrombosis were neurotologic in nature. One case presented with a sudden onset unilateral facial paralysis; another case presented with pressure/fullness sensation in one ear accompanied by nausea and vomiting. Clinical presentation and evaluation of these cases is presented, with a discussion of symptom etiology. Recommended non-invasive medical management methods are discussed. Cases in which the thrombosis involves the sigmoid, transverse, and sagittal sinuses should be suspect for etiologic sources beyond the ear even when the presenting symptoms are neurotologic in nature. Management of these cases is different from that of an otogenic sigmoid sinus thrombosis. A complete medical history taken from women of child bearing age should include the use of oral contraceptives, which may be suspect for inducing intracranial venous thromboses.

[Do neomycin ointment dressings damage the inner-ear when used in the external auditory canal or the radical mastoidectomy cavity? (author's transl)]. / Wird das Innenohr durch eine neomycinhaltige Salbenstreifentamponade im äusseren Gehörgang oder im Mittelohr gefährdet?

When in low concentration (0.38%) in an ointment base neomycin within the middle ear does not damage the inner ear. Animal experiments show that doses 10 times greater do not damage the hair cells, but when in aqueous solution all hair cells are destroyed. Many years experience has confirmed that neomycin ointment packing for postoperative ears and infected radical mastoid cavities does not produce inner ear damage. These patients have been carefully monitored by audiometry.